chr15-71164148-T-C

Variant names:

• chr15-71164148-T-C
• rs590050
• NM_024817.3:c.99+9216T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024817.3(THSD4):​c.99+9216T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 141,348 control chromosomes in the GnomAD database, including 7,754 homozygotes. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (7754 hom., cov: 27)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549
• Publications: 2 publications found

Genes affected

THSD4 (HGNC:25835): (thrombospondin type 1 domain containing 4) Predicted to enable hydrolase activity. Predicted to be an extracellular matrix structural constituent. Predicted to act upstream of or within elastic fiber assembly. Located in collagen-containing extracellular matrix and extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

HMGB1P6 (HGNC:4998): (high mobility group box 1 pseudogene 6)

THSD4-AS1 (HGNC:51420): (THSD4 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD4	NM_024817.3	c.99+9216T>C		intron_variant	Intron 3 of 17	ENST00000261862.8	NP_079093.2
HMGB1P6		n.71164148T>C		intragenic_variant
THSD4	NM_001394532.1	c.99+9216T>C		intron_variant	Intron 3 of 17		NP_001381461.1
THSD4	XM_047433080.1	c.99+9216T>C		intron_variant	Intron 3 of 17		XP_047289036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8	c.99+9216T>C		intron_variant	Intron 3 of 17	5	NM_024817.3	ENSP00000261862.8

Frequencies

GnomAD3 genomes AF: 0.257 AC: 36327 AN: 141254 Hom.: 7723 Cov.: 27

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.0783

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0731

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.202

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.258 AC: 36401 AN: 141348 Hom.: 7754 Cov.: 27 AF XY: 0.253 AC XY: 17429 AN XY: 68764

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.583 AC: 21658 AN: 37142

American (AMR) AF: 0.126 AC: 1831 AN: 14526

Ashkenazi Jewish (ASJ) AF: 0.0731 AC: 247 AN: 3380

East Asian (EAS) AF: 0.399 AC: 1699 AN: 4258

South Asian (SAS) AF: 0.217 AC: 924 AN: 4250

European-Finnish (FIN) AF: 0.118 AC: 1127 AN: 9582

Middle Eastern (MID) AF: 0.130 AC: 36 AN: 276

European-Non Finnish (NFE) AF: 0.129 AC: 8409 AN: 65074

Other (OTH) AF: 0.203 AC: 400 AN: 1966

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0500 Hom.: 41

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.1
DANN	Benign	0.89
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs590050; hg19: chr15-71456487;